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Protein

Ecto-NOX disulfide-thiol exchanger 2

Gene

ENOX2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May be involved in cell growth. Probably acts as a terminal oxidase of plasma electron transport from cytosolic NAD(P)H via hydroquinones to acceptors at the cell surface. Hydroquinone oxidase activity alternates with a protein disulfide-thiol interchange/oxidoreductase activity which may control physical membrane displacements associated with vesicle budding or cell enlargement. The activities oscillate with a period length of 22 minutes and play a role in control of the ultradian cellular biological clock.2 Publications

Cofactori

Cu cation1 Publication

Enzyme regulationi

Inhibited by the antitumor sulfonylurea LY181984, the vabilloid capsaicin, and retinoids.3 Publications

GO - Molecular functioni

GO - Biological processi

  • cell growth Source: UniProtKB
  • oxidation-reduction process Source: UniProtKB
  • regulation of growth Source: UniProtKB-KW
  • ultradian rhythm Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Biological rhythms, Electron transport, Growth regulation, Transport

Keywords - Ligandi

Copper, NAD

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165675-MONOMER.
SIGNORiQ16206.

Names & Taxonomyi

Protein namesi
Recommended name:
Ecto-NOX disulfide-thiol exchanger 2
Alternative name(s):
APK1 antigen
Cytosolic ovarian carcinoma antigen 1
Tumor-associated hydroquinone oxidase
Short name:
tNOX
Including the following 2 domains:
Hydroquinone [NADH] oxidase (EC:1.-.-.-)
Protein disulfide-thiol oxidoreductase (EC:1.-.-.-)
Gene namesi
Name:ENOX2
Synonyms:COVA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:2259. ENOX2.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: ProtInc
  • external side of plasma membrane Source: UniProtKB
  • extracellular space Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi396M → A: No effect on activity but response to capsaicin is lost. 1 Publication1
Mutagenesisi505C → A: No effect on activity. 1 Publication1
Mutagenesisi510C → A: Loss of activity. 1 Publication1
Mutagenesisi546H → A: Loss of activity. 1 Publication1
Mutagenesisi558C → A: Period length of activity extended to 42 minutes. 1 Publication1
Mutagenesisi562H → A: Loss of activity. 1 Publication1
Mutagenesisi569C → A: Loss of activity. 1 Publication1
Mutagenesisi575C → A: Period length of activity extended to 36 minutes. 1 Publication1
Mutagenesisi592G → V: Loss of activity. 1 Publication1
Mutagenesisi602C → A: Period length of activity extended to 36 minutes. 1 Publication1

Organism-specific databases

DisGeNETi10495.
OpenTargetsiENSG00000165675.
PharmGKBiPA162385106.

Polymorphism and mutation databases

BioMutaiENOX2.
DMDMi34978371.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000792751 – 610Ecto-NOX disulfide-thiol exchanger 2Add BLAST610

Post-translational modificationi

Glycosylated.1 Publication

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiQ16206.
PaxDbiQ16206.
PeptideAtlasiQ16206.
PRIDEiQ16206.

PTM databases

iPTMnetiQ16206.
PhosphoSitePlusiQ16206.

Expressioni

Tissue specificityi

Found in the sera of cancer patients with a wide variety of cancers including breast, prostate, lung and ovarian cancers, leukemias, and lymphomas. Not found in the serum of healthy volunteers or patients with disorders other than cancer. Probably shed into serum by cancer cells. Found on the cell borders of renal, kidney and ovarian carcinomas but not on the borders of surrounding non-cancerous stromal cells.

Gene expression databases

BgeeiENSG00000165675.
CleanExiHS_ENOX2.
ExpressionAtlasiQ16206. baseline and differential.
GenevisibleiQ16206. HS.

Organism-specific databases

HPAiHPA000514.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
CIB3Q96Q773EBI-10179508,EBI-10292696
ENOX1Q8TC923EBI-10179508,EBI-713221
MAGEA11P43364-23EBI-10179508,EBI-10178634
MLLT6Q6P2C63EBI-10179508,EBI-5773143
SNRPAP090123EBI-10179508,EBI-607085
TRAF5O004633EBI-10179508,EBI-523498

Protein-protein interaction databases

BioGridi115758. 12 interactors.
IntActiQ16206. 12 interactors.
MINTiMINT-4825886.
STRINGi9606.ENSP00000337146.

Structurei

3D structure databases

ProteinModelPortaliQ16206.
SMRiQ16206.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini128 – 207RRMPROSITE-ProRule annotationAdd BLAST80

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili293 – 328Sequence analysisAdd BLAST36
Coiled coili381 – 505Sequence analysisAdd BLAST125

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi58 – 125Pro-richAdd BLAST68

Sequence similaritiesi

Belongs to the ENOX family.Curated
Contains 1 RRM (RNA recognition motif) domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiENOG410ITYH. Eukaryota.
ENOG4110UUI. LUCA.
GeneTreeiENSGT00390000006788.
HOVERGENiHBG051083.
InParanoidiQ16206.
OMAiRNANNFY.
OrthoDBiEOG091G038C.
PhylomeDBiQ16206.
TreeFamiTF323802.

Family and domain databases

Gene3Di3.30.70.330. 1 hit.
InterProiIPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamiPF00076. RRM_1. 1 hit.
[Graphical view]
SMARTiSM00360. RRM. 1 hit.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 1 hit.
PROSITEiPS50102. RRM. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q16206-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MQRDFRWLWV YEIGYAADNS RTLNVDSTAM TLPMSDPTAW ATAMNNLGMA
60 70 80 90 100
PLGIAGQPIL PDFDPALGMM TGIPPITPMM PGLGIVPPPI PPDMPVVKEI
110 120 130 140 150
IHCKSCTLFP PNPNLPPPAT RERPPGCKTV FVGGLPENGT EQIIVEVFEQ
160 170 180 190 200
CGEIIAIRKS KKNFCHIRFA EEYMVDKALY LSGYRIRLGS STDKKDTGRL
210 220 230 240 250
HVDFAQARDD LYEWECKQRM LAREERHRRR MEEERLRPPS PPPVVHYSDH
260 270 280 290 300
ECSIVAEKLK DDSKFSEAVQ TLLTWIERGE VNRRSANNFY SMIQSANSHV
310 320 330 340 350
RRLVNEKAAH EKDMEEAKEK FKQALSGILI QFEQIVAVYH SASKQKAWDH
360 370 380 390 400
FTKAQRKNIS VWCKQAEEIR NIHNDELMGI RREEEMEMSD DEIEEMTETK
410 420 430 440 450
ETEESALVSQ AEALKEENDS LRWQLDAYRN EVELLKQEQG KVHREDDPNK
460 470 480 490 500
EQQLKLLQQA LQGMQQHLLK VQEEYKKKEA ELEKLKDDKL QVEKMLENLK
510 520 530 540 550
EKESCASRLC ASNQDSEYPL EKTMNSSPIK SEREALLVGI ISTFLHVHPF
560 570 580 590 600
GASIEYICSY LHRLDNKICT SDVECLMGRL QHTFKQEMTG VGASLEKRWK
610
FCGFEGLKLT
Length:610
Mass (Da):70,082
Last modified:September 19, 2003 - v2
Checksum:iC30BC45730B62A57
GO
Isoform 2 (identifier: Q16206-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-29: Missing.

Show »
Length:581
Mass (Da):66,621
Checksum:iA0252986B74DC11C
GO

Sequence cautioni

The sequence AAB30428 differs from that shown. Reason: Frameshift at positions 302 and 357.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti123R → G in AK000353 (PubMed:14702039).Curated1
Sequence conflicti311E → G in AK000353 (PubMed:14702039).Curated1
Sequence conflicti326S → V AA sequence (PubMed:11437345).Curated1
Sequence conflicti328I → V AA sequence (PubMed:11437345).Curated1
Sequence conflicti332F → A AA sequence (PubMed:11437345).Curated1
Sequence conflicti406 – 407Missing in AAH19254 (PubMed:15489334).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069427202V → I.1 PublicationCorresponds to variant rs754363472dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0157191 – 29Missing in isoform 2. 1 PublicationAdd BLAST29

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF207881 mRNA. Translation: AAF20934.2.
AK000353 mRNA. No translation available.
AK289837 mRNA. Translation: BAF82526.1.
AK289812 mRNA. Translation: BAF82501.1.
AL049733, AL591908 Genomic DNA. Translation: CAI43113.1.
AL049733, AL591908 Genomic DNA. Translation: CAI43114.1.
AL591908, AL049733 Genomic DNA. Translation: CAH71675.1.
AL591908, AL049733 Genomic DNA. Translation: CAH71676.1.
CH471107 Genomic DNA. Translation: EAX11796.1.
CH471107 Genomic DNA. Translation: EAX11797.1.
BC019254 mRNA. Translation: AAH19254.2.
BC140874 mRNA. Translation: AAI40875.1.
AL133207 mRNA. Translation: CAB61581.2.
S72904 mRNA. Translation: AAB30428.1. Frameshift.
CCDSiCCDS14626.1. [Q16206-1]
CCDS14627.1. [Q16206-2]
PIRiI54780.
RefSeqiNP_001268665.1. NM_001281736.1. [Q16206-2]
NP_006366.2. NM_006375.3. [Q16206-2]
NP_872114.1. NM_182314.2. [Q16206-1]
XP_005262411.1. XM_005262354.3. [Q16206-1]
XP_011529549.1. XM_011531247.2. [Q16206-1]
XP_011529551.1. XM_011531249.2. [Q16206-1]
XP_011529553.1. XM_011531251.2. [Q16206-2]
XP_016884715.1. XM_017029226.1. [Q16206-1]
XP_016884716.1. XM_017029227.1. [Q16206-1]
XP_016884717.1. XM_017029228.1. [Q16206-1]
UniGeneiHs.171458.

Genome annotation databases

EnsembliENST00000338144; ENSP00000337146; ENSG00000165675. [Q16206-1]
ENST00000370927; ENSP00000359965; ENSG00000165675. [Q16206-1]
ENST00000370935; ENSP00000359973; ENSG00000165675. [Q16206-2]
ENST00000394363; ENSP00000377890; ENSG00000165675. [Q16206-2]
GeneIDi10495.
KEGGihsa:10495.
UCSCiuc004evw.5. human. [Q16206-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF207881 mRNA. Translation: AAF20934.2.
AK000353 mRNA. No translation available.
AK289837 mRNA. Translation: BAF82526.1.
AK289812 mRNA. Translation: BAF82501.1.
AL049733, AL591908 Genomic DNA. Translation: CAI43113.1.
AL049733, AL591908 Genomic DNA. Translation: CAI43114.1.
AL591908, AL049733 Genomic DNA. Translation: CAH71675.1.
AL591908, AL049733 Genomic DNA. Translation: CAH71676.1.
CH471107 Genomic DNA. Translation: EAX11796.1.
CH471107 Genomic DNA. Translation: EAX11797.1.
BC019254 mRNA. Translation: AAH19254.2.
BC140874 mRNA. Translation: AAI40875.1.
AL133207 mRNA. Translation: CAB61581.2.
S72904 mRNA. Translation: AAB30428.1. Frameshift.
CCDSiCCDS14626.1. [Q16206-1]
CCDS14627.1. [Q16206-2]
PIRiI54780.
RefSeqiNP_001268665.1. NM_001281736.1. [Q16206-2]
NP_006366.2. NM_006375.3. [Q16206-2]
NP_872114.1. NM_182314.2. [Q16206-1]
XP_005262411.1. XM_005262354.3. [Q16206-1]
XP_011529549.1. XM_011531247.2. [Q16206-1]
XP_011529551.1. XM_011531249.2. [Q16206-1]
XP_011529553.1. XM_011531251.2. [Q16206-2]
XP_016884715.1. XM_017029226.1. [Q16206-1]
XP_016884716.1. XM_017029227.1. [Q16206-1]
XP_016884717.1. XM_017029228.1. [Q16206-1]
UniGeneiHs.171458.

3D structure databases

ProteinModelPortaliQ16206.
SMRiQ16206.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115758. 12 interactors.
IntActiQ16206. 12 interactors.
MINTiMINT-4825886.
STRINGi9606.ENSP00000337146.

PTM databases

iPTMnetiQ16206.
PhosphoSitePlusiQ16206.

Polymorphism and mutation databases

BioMutaiENOX2.
DMDMi34978371.

Proteomic databases

MaxQBiQ16206.
PaxDbiQ16206.
PeptideAtlasiQ16206.
PRIDEiQ16206.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338144; ENSP00000337146; ENSG00000165675. [Q16206-1]
ENST00000370927; ENSP00000359965; ENSG00000165675. [Q16206-1]
ENST00000370935; ENSP00000359973; ENSG00000165675. [Q16206-2]
ENST00000394363; ENSP00000377890; ENSG00000165675. [Q16206-2]
GeneIDi10495.
KEGGihsa:10495.
UCSCiuc004evw.5. human. [Q16206-1]

Organism-specific databases

CTDi10495.
DisGeNETi10495.
GeneCardsiENOX2.
HGNCiHGNC:2259. ENOX2.
HPAiHPA000514.
MIMi300282. gene.
neXtProtiNX_Q16206.
OpenTargetsiENSG00000165675.
PharmGKBiPA162385106.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ITYH. Eukaryota.
ENOG4110UUI. LUCA.
GeneTreeiENSGT00390000006788.
HOVERGENiHBG051083.
InParanoidiQ16206.
OMAiRNANNFY.
OrthoDBiEOG091G038C.
PhylomeDBiQ16206.
TreeFamiTF323802.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000165675-MONOMER.
SIGNORiQ16206.

Miscellaneous databases

ChiTaRSiENOX2. human.
GeneWikiiENOX2.
GenomeRNAii10495.
PROiQ16206.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000165675.
CleanExiHS_ENOX2.
ExpressionAtlasiQ16206. baseline and differential.
GenevisibleiQ16206. HS.

Family and domain databases

Gene3Di3.30.70.330. 1 hit.
InterProiIPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamiPF00076. RRM_1. 1 hit.
[Graphical view]
SMARTiSM00360. RRM. 1 hit.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 1 hit.
PROSITEiPS50102. RRM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiENOX2_HUMAN
AccessioniPrimary (citable) accession number: Q16206
Secondary accession number(s): A8K197
, A8K1C2, Q5VTJ1, Q5VTJ2, Q8WUX0, Q9NTP6, Q9UH82
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: September 19, 2003
Last modified: November 2, 2016
This is version 145 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Has several properties associated with prions including resistance to proteases, resistance to cyanogen bromide digestion, and the ability to form amyloid filaments resembling those of spongiform encephalopathies.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.